The PRORATA study. A multi-centre study based in France. Unblinded, randomised controlled trial comparing strategy utilising serum procalcitonin measurement to guide initiation and cessation of antibiotics for ICU patients with suspected bacterial infection, with antibiotic administration according to an agreed guideline

Participants

630 adult ICU patients (8 medical, surgical or medical-surgical ICUs; 6 hospitals). Mean age was 62; 66% male; SAPS II 47; SOFA score 7.8) with suspected bacterial infection (either at admission or during ICU stay). 89% patients were medical.16% enrolled patients were defined as being "Immunocompromised" (including patients with AIDS, solid organ transplant, haematological malignancy, prior chemotherapy or radiotherapy, and long-term corticosteroid or other immunosuppressant therapy); identifying and excluding data from these patients for the purpose of the systematic review was not possible. There appear not to have been significant differences in baseline characteristics between treatment groups. Of 621 patients entered into the analysis, 214 (34%) had VAP or "HAP": 141 (23%) patients were diagnosed with VAP, and 73 (12%) patients had HAP not requiring mechanical ventilation. For all patients with microbiologically-confirmed infection, initial antibiotic therapy was appropriate in 92% cases. Diagnostic criteria for VAP and HAP were not provided in the full-text article

Patients randomised to intervention group (311 randomised; 4 withdrew consent; 307 included in analysis; 75 patients with VAP; 29 with HAP not requiring mechanical ventilation) had serum procalcitonin level measured at inclusion, at each infectious episode until day 28, and for every morning that antibiotics were administered. The guidance for withholding or stopping antibiotic therapy was: i. antibiotics to be withheld when procalcitonin was < 0.5 µg/L on day of study entry; ii. antibiotics to be discontinued when procalcitonin level had fallen to < 0.5 µg/L or to less than 20% of the peak procalcitonin concentration

For patients randomised to control group (319 randomised; 4 withdrew; 1 randomised twice; 314 included in analysis; 66 patients with VAP; 44 patients with HAP not requiring mechanical ventilation), physicians were encouraged to administer antibiotics according to agreed recommendations (including duration of therapy)

Outcomes

Most outcome data were presented for all patients, without specific reference to patients with VAP or HAP (non-ventilated)

For patients specifically with VAP, the following outcomes were presented:

Duration of first episode of antibiotic treatment

Number of days without antibiotics (28-day)

Mortality (28-day)

Notes

Procalcitonin measurements were used to guide whether to initiate antibiotic therapy as well as when to discontinue therapy. A very low proportion of recruited patients were surgical, which may limit generalisability of results. There was a high incidence of protocol non-adherence; the algorithm for antimicrobial therapy administration was not followed (overall) in 162 patients (53%) in the intervention group, nor for 141 patients in the control group (45%). For all patients, a non-significant increase in 60-day mortality was observed in the procalcitonin group (92/307 (30%) versus 82/ 314 (26.1%)] in the control group). Furthermore, the study may have been under-powered to determine non-inferiority of PCT-guided therapy in terms of death, since it was based upon a 35% absolute mortality in the control group and a 10% between-group mortality difference. For all patients, in the procalcitonin group there were non-significantly greater relapse rates (20/ 307 (6.5%) versus 16/ 314 (5.1%) in control group; P = 0.45) and superinfection rates (106/ 307 (34.5%) versus 97/ 314 (30.9%) in the control group; P = 0.29)

401 adult patients. 51 French ICUs. 72% male; mean age 61; episodes due to NF-GNB 32.5%, MRSA 11.2%; mean SAPS II score 45; mean SOFA score 7.4 at admission. VAP was diagnosed according to the following criteria: new and persistent radiographic infiltrate, plus 1 of: purulent tracheal secretions, temperature of 38.4 °C or higher, or leukocyte count > 10,000/µL; and positive quantitative culture of 104 cfu/mL from BAL or 103 cfu/mL from PSB. Duration of mechanical ventilation prior to VAP: 13.6 days. No significant differences between groups at baseline, with the exception of significantly higher proportion of men (76.6%) in 8-day regimen versus men in 15-day regimen (67.6%; P = 0.046). All patients received appropriate initial antibiotics. Exclusions included early onset pneumonia (within 5 days of commencing mechanical ventilation) in patients who had received no antimicrobial therapy in the 15 days prior to diagnosis of pneumonia, and immunocompromised state, characterised by: neutropenia, AIDS, long-term corticosteroids or other immunosuppressant therapy

Repeat bronchoscopy was performed on the basis of fever, purulent secretions, new or progressive pulmonary infiltrates, or deterioration in respiratory or haemodynamic parameters. It was not performed routinely, e.g. on completion of 8-day course of therapy, and consequently data regarding persistent colonisation with NF-GNB is not available

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Randomisation was performed...and stratified... according to a computer-generated random-number table."

Allocation concealment (selection bias)

Low risk

"Randomisation performed centrally, using an interactive voice system... randomisation was not communicated to the investigators until day 8... On that day, investigators had to telephone the randomisation centre to receive the treatment assignment by fax."

Blinding (performance bias and detection bias) All outcomes

High risk

"...Patients, medical and nursing staffs, and pharmacists remained blinded until [day 8]." However, importantly, no attempt was made to blind from day 8, i.e. the point from which thereafter allocation might make a significant difference

Incomplete outcome data (attrition bias) All outcomes

Low risk

Following randomisation, 0 patients were lost to follow-up. 1 patient excluded from analysis following withdrawal of consent

Selective reporting (reporting bias)

Unclear risk

Study protocol not available for examination. However, outcome measures are those expected and appropriately presented within the report

Other bias

Low risk

There was a significantly higher proportion of men in the 8-day group (76.6%) compared with the 15-day group (67.6%; P = 0.046). However, there were not significant differences in illness severity scores, prior duration of mechanical ventilation, prior antibiotic administration, micro-organisms responsible for VAP, and antibiotic regimes to treat VAP

Data regarding proportions of patients who contrary to protocol did not receive a full 8-day or 15-day course of antibiotics are not provided. However, absolute antibiotic-treatment days and 28-day antibiotic-free day data indicates significantly less antibiotic exposure as a consequence of allocation to short or prolonged-course therapy

Exclusions include: second episode of pneumonia during single hospitalisation, terminal illness, failure to isolate bacterial growth

30 patients randomised from 39 patients with clinical features of VAP: 9 not enrolled because of terminal illness or failure to isolate bacteria

Interventions

14 patients randomised to receive 7-day course of antibiotics; 16 patients to receive 16-day course. Choice of antibiotic: on microbiology advice, taking into account whether early (up to including 5 days after commencing mechanical ventilation) or late-onset VAP, and whether risk factors for multi-resistant bacteria present, and modified according to culture/sensitivity results

94% patients received appropriate initial antibiotic therapy

Outcomes

The following outcome measures were presented:

Mortality (14-day and 28-day)

Antibiotic-free days (28-day)

Microbiological resolution (timescale not specified)

CPIS resolution (days 1, 10, 14)

Mechanical ventilation-free days (28-day)

Recurrence: relapse or super-infection (timescale not specified)

Duration of ITU stay

Notes

Data regarding protocol violations and patients lost to follow-up not available. Unable to make contact trial with authors to request supplementary information

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Use of random number table

Allocation concealment (selection bias)

Unclear risk

Inadequately reported

Blinding (performance bias and detection bias) All outcomes

Unclear risk

Inadequately reported

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

Inadequately reported

Selective reporting (reporting bias)

Unclear risk

Inadequately reported

Other bias

Low risk

No evidence of other source of bias

Medina 2007

Methods

2 centre study, based in Uruguay, conducted May 2003 to December 2006 (during the period December 2005 to April 2006 recruitment was interrupted while eligible patients were enrolled in the Pontet 2007 study). Randomised controlled study comparing fixed short (8-day) and long (12-day) courses of antibiotic therapy for VAP.

Participants

77 patients (medical, surgical and neurosurgical; mean age 59 years, 53% male, 63.6% NF-GNB, 9.1% MRSA; median APACHE II score 21, MODS score 5, SOFA score 6) with VAP. VAP was diagnosed on the basis of: new and persistent radiographic infiltrates, 2 of temperature ≥38.5 ºC or <36 ºC, leukocytes ≥12,000/ mm3 or ≤ 4 x103/ mm3, and BAL culture ≥ 104 cfu/ml, or positive ETA plus CPIS > 6, or micro-organism in ≥ 2 blood cultures with identical sensitivity to tracheal secretions and in absence of other possible infection, or positive culture of pleural fluid. Mean time after commencing mechanical ventilation before onset of VAP: 9.3 days. 68% patients had received a prior course of antibiotics. In 97% cases, initial antibiotic therapy for VAP was appropriate. There were no significant differences in baseline characteristics between treatment groups Exclusion criteria: failure to meet clinical and microbiological criteria, decision not to institute antibiotic therapy, duration of therapy < 6 days, death before 6th day of treatment, onset of VAP within 48 hours of admission from other centre

Interventions

77 patients randomised to 8-day treatment or 12-day course on Day 8 of antibiotic therapy. Antibiotic choice was that of the attending physician; in 75/77 (97%) cases, initial antibiotic therapy was appropriate. The most commonly used antibiotics were: cefoperazone-sulbactam, carbapenem and other third-generation cephalosporins. In 51% cases, antibiotic combinations were used

Outcomes

The following outcomes were studied:

ITU mortality

VAP-related mortality

Clinical resolution of VAP

Non-resolution of VAP ("Therapeutic failure")

Recurrence of VAP

Duration of mechanical ventilation

Notes

0 patients were lost to follow-up. No patient received a shorter duration of antibiotic therapy than allocated; data incomplete for patients who had antibiotics continued beyond the allocated duration

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Block randomisation using random number table

Allocation concealment (selection bias)

Low risk

Sealed, numbered envelopes opened sequentially

Blinding (performance bias and detection bias) All outcomes

High risk

Unblinded study

Incomplete outcome data (attrition bias) All outcomes

Low risk

No patients lost to follow-up

Selective reporting (reporting bias)

Unclear risk

Unclear. Data incomplete for patients who had antibiotics continued beyond the allocated duration

Exclusions: transfers to host institution because of lack of capacity at external institutions

Interventions

154 patients randomised to discontinuation group; one of investigators recommended discontinuation of antibiotics to treating physician on weekdays if: non-infectious cause for radiographic infiltrates identified, signs and symptoms of active infection had resolved (in terms of temperature, white cell count, radiographic appearance, sputum characteristics and PaO2/ FiO2 ratio). 148 patients were randomised to the control group. Recommendations regarding choice of antibiotic therapy were made to both groups

Outcomes

Reported outcome measures:

Duration of antibiotic therapy for VAP

ITU mortality

Hospital mortality

Duration of ITU stay

Duration of hospital stay

Duration of mechanical ventilation

VAP recurrence during same ITU stay

Notes

Outcome data was missing for 4 patients in the intervention group, and for 8 patients in the control group. Among intervention group, recommendations to discontinue antibiotics were given to the physicians of 142 patients (94.7%); among 88.7% of these patients antibiotics were discontinued within 48 hours of the recommendation. Trial author contacted, but no further information available

4-centre Uruguayan study, conducted December 2005 to April 2006; 2 of these centres also recruited to the study Medina 2007, but outside this time period. Unblinded, randomised controlled study comparing PCT-guided strategy for antibiotic cessation versus standard therapy for VAP

Participants

81 adult patients (medical, surgical, cardiothoracic and neurosurgical; mean age 54 years, 63% male; NF-GNB 23.4%; MRSA 6.1%; Day 1 MODS 6.2; Day 1 SOFA score 4.8) with suspected VAP. VAP was diagnosed on the basis of: new and persistent radiographic infiltrates, 2 of temperature ≥ 38.5 ºC or < 36 ºC, leukocytes ≥12,000/ mm3 or ≤ 4 x103/ mm3, and BAL culture ≥ 104 cfu/ml, or positive ETA plus CPIS > 6, or micro-organism in ≥ 2 blood cultures with identical sensitivity to tracheal secretions and in absence of other possible infection, or positive culture of pleural fluid. Patients were excluded on the basis of: AIDS, leukaemia or immunosuppression. A further 14 patients were excluded after randomisation; from control group, 5 patients were excluded because of short duration of treatment (3 patients) or negative BAL (3 patients); from the PCT group, 9 patients were excluded post-randomisation because Day 1 or 2 PCT was < 0.5 ng/mL. There were no significant baseline differences between groups in terms of demographics, underlying disease or prior antibiotic administration

Interventions

Intervention: for the group receiving PCT-guided therapy; if at day 7 PCT was < 0.5 ng/ml, antibiotic discontinuation was encouraged. Duration of therapy in control group was according to pre-existing guidelines in place at each ICU. Choice of antibiotic therapy was that of the treating physician. Most commonly used antibiotics were: cephalosporins, ampicillin-sulbactam and amikacin; antibiotic combinations were used in 54.5% cases

Outcomes

Data are presented as a per-protocol analysis. The following outcome measures were reported:

ITU mortality

VAP-related ITU mortality

Duration of mechanical ventilation

Duration of ITU stay

Non-resolution (therapeutic failure)

Relapse (Day 29)

Super-infection (Day 29)

Clinical resolution

CPIS (Day 1, 7)

MODS (Day 1, 7)

SOFA score (Day 1, 7)

Notes

All patients in the procalcitonin group completed at least 7 days of antibiotic therapy. At Day 7, antibiotics were discontinued for all patients with procalcitonin < 0.5 ng/ml

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Block randomisation using random number table

Allocation concealment (selection bias)

Low risk

Sealed, numbered envelopes opened in sequence

Blinding (performance bias and detection bias) All outcomes

High risk

Treating team were made aware of assignment on Day 7, when PCT measured and communicated to PCT group

Incomplete outcome data (attrition bias) All outcomes

Low risk

No patients lost to follow-up

Selective reporting (reporting bias)

Unclear risk

Unclear

Other bias

High risk

Potential source of bias as this is a per-protocol analysis; exclusion of 9 patients with low PCT measurements in the PCT group may exclude a higher proportion of relatively well patients compared with the control group

Randomised at Day 1 of episode of possible pneumonia. Intervention group (N = 39): 3 days' ciprofloxacin monotherapy. At Day 3 if CPIS < 7, antibiotics would be discontinued; if CPIS > 6, therapy would be continued, with choice of agent and duration of therapy at the discretion of treating physician, and incorporating microbiology results

For patients allocated to the short-course therapy, 0 patients with CPIS < 7 at Day 3 had antibiotics continued beyond 72 hours

A significant decrease in duration of therapy in "Standard therapy" group was observed with time (P = 0.0001), thought to be a result of unblinded nature of study. The study was terminated by institutional review board as it was deemed "unethical to continue study."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Randomisation/concealment not described

Blinding (performance bias and detection bias) All outcomes

High risk

This was an unblinded study

Incomplete outcome data (attrition bias) All outcomes

Low risk

No missing outcome data

Selective reporting (reporting bias)

High risk

The components of the composite measure of "emergence of antimicrobial resistance or superinfection" are not reported

Other bias

High risk

Stopped early by institutional review board. Results for patients managed in "experimental" group appear to have influenced management of patients subsequently allocated to "standard therapy group"

101 patients were randomised on day of diagnosis of VAP (Day 0). Serum procalcitonin levels were measured from Day 0 to Day 10 for all patients (including patients in the control group). For the 51 patients in the intervention group, discontinuation of antibiotic therapy was encouraged according to an algorithm 72 hours (Day 2) after randomisation if PCT was < 0.5 µg/L or had decreased to 20% or less of level on Day 0

For the 50 patients randomised to the control group, procalcitonin levels were withheld, and duration of therapy was determined by treating physician

In both intervention and control groups, choice of antibiotic therapy was that of the attending physician

Outcomes

The following outcome measures were reported:

Mortality (Day 28)

In-hospital mortality

Duration of antibiotic therapy

Antibiotic-free days (Day 28)

Mechanical ventilation-free days (Day 28)

Duration of hospital stay

Number of ITU-free days alive (Day 28)

Clinical features associated with respiratory infection

PaO2/ FiO2

SOFA score

ODIN score

CPIS

Notes

It is unclear how many patients were treated with antibiotics beyond the point at which discontinuation was advocated by the protocol

This 2-by-2 factorial randomised controlled study aiming to compare: i. invasive and non-invasive diagnostic strategies for diagnosis of VAP, and ii. initial empiric treatment with meropenem or meropenem plus ciprofloxacin for suspected VAP. There was no significant difference in number of antibiotic-free days between groups of patients allocated to invasive or non-invasive strategies

This was a randomised study designed to compare strategies for diagnosis and selection of initial antimicrobial therapy of VAP, not duration of therapy. For groups of patients randomised to both invasive and non-invasive diagnostic strategies, recommended duration of therapy in the presence of positive respiratory culture (i.e. confirmed pneumonia) was 14 days

Hochreiter 2009

This was a randomised controlled study comparing a strategy using serial procalcitonin (PCT) measurement to guide discontinuation of antibiotic therapy for treatment of sepsis in 110 surgical intensive care patients with standard therapy. Of these patients, 43 had "pneumonia"; it is unclear what proportion had nosocomial or community-acquired pneumonia, and what proportion of patients was receiving mechanical ventilation at time of diagnosis. Duration of antibiotic therapy was significantly shorter in the intervention (PCT-guided) group (5.9 +/- 1.7 days versus 7.9 +/- 0.5 days), but outcome data relevant to this systematic review are restricted to duration of ITU stay and hospital mortality

This was an RCT investigating effectiveness of an antibiotic de-escalation protocol for patients with low probability of HAP (according to CPIS and culture results), published in abstract form only. It has not been possible to contact study authors for further details. It is unclear whether it was a single or multi-centre study. 109 patients (unclear whether exclusively adults or not) with HAP (diagnostic criteria not described) were randomised to the de-escalation protocol (N = 54) or standard therapy (N = 55). The protocol is not described nor relevant outcome data presented adequately for inclusion in this review. In addition, the significantly higher rate of appropriate initial antibiotic therapy in the de-escalation group represents a potential risk of bias

This multi-centre randomised controlled study from Mexico enrolled 65 patients in a study intended to evaluate a strategy of early discontinuation of empirical antibiotic therapy: it has been published in abstract form only. 31 patients were allocated to early (< 8 days) discontinuation of empirical therapy versus 34 patients to late discontinuation (> 9 days). Patient characteristics and diagnostic criteria were not described. Outcome data presented in the abstract was inadequate for the study's inclusion in this review, and contact with a trial author did not yield any further information. Furthermore, a highly significant risk of bias was identified: antibiotic discontinuation at Day 8 was higher (70.6%) among patients allocated to late discontinuation than among patients allocated to early discontinuation (67.7%)

Nobre 2008

This was a randomised controlled study comparing a strategy using serial measurements of procalcitonin (PCT) to guide cessation of antibiotic therapy with standard therapy in critically ill patients with sepsis or septic shock. 79 patients were randomised, of whom a total of 47 patients had sepsis of pulmonary origin. A high proportion of patients (68%) had community-acquired sepsis. A significant proportion of patients in the PCT group (19%) had the protocol overridden to receive a longer course of antibiotics than advised by the algorithm. On intention-to-treat analysis, the difference in antibiotic days between control and intervention groups for all patients was not significant. A decision was made to exclude this study on the basis of small numbers of the subgroup of patients with suspected HAP or VAP and the lack of significant difference between groups in terms of duration of therapy

Peery 2001

This was a randomised study comparing diagnostic strategies for suspected VAP. It was not designed to investigate duration of therapy; there were no protocols to guide duration of antibiotic therapy

Rello 2004

This was an observational rather than a randomised controlled study. It investigated outcomes following introduction of a "De-escalation" strategy which incorporated the initial administration of broad spectrum antibiotics and subsequent simplification of antibiotic treatment with culture results: 1. changing to monotherapy in absence of Pseudomonas sp; 2. shortening therapy to < 5 days if culture negative and > 48 hours of defervescence; 3. changing from broad to narrow spectrum agent on basis of culture results

Sanchez-Nieto 1998

A randomised clinical trial comparing the effects of an invasive quantitative diagnostic strategy versus a non-invasive strategy on management of and outcome from suspected VAP

Schroeder 2007

This was a RCT comparing a procalcitonin-guided antibiotic discontinuation strategy with standard treatment for surgical intensive care patients with severe sepsis. The reasons for exclusion of this study are: 1. its very small size (of the 27 patients enrolled in this study, only 8 were diagnosed with pneumonia); 2. it is unclear what proportion of patients had nosocomial versus community-acquired infection; 3. of the patients with "pneumonia" it is unclear what proportion were receiving mechanical ventilation at time of diagnosis; 4. limited outcome data relevant to this systematic review are published (in-hospital mortality and duration of ICU stay)

Summary of findings for the main comparison. Should short (fixed duration)-course antibiotic therapy versus prolonged-course antibiotic therapy be used for critically ill patients with hospital-acquired pneumonia?

Should short (fixed duration)-course antibiotic therapy versus prolonged-course antibiotic therapy be used for critically ill patients with hospital-acquired pneumonia?

The mean 28-day antibiotic-free days in the intervention groups was 4.02 higher(2.26 to 5.78 higher)

431 (2 studies)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MRSA: methicillin-resistant Staphylococcus aureus; NF-GNB: non-fermenting Gram-negative bacilli; OR: odds ratio

GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Summary of findings 2. Discontinuation of antibiotics according to Clinical Pulmonary Infection Score for critically ill adults with hospital-acquired pneumonia

Discontinuation of antibiotics according to Clinical Pulmonary Infection Score for critically ill adults with hospital-acquired pneumonia

Discontinuation of antibiotics according to Clinical Pulmonary Infection Score

30-day mortality

Study population

OR 0.33(0.1 to 1.03)

81 (1 study)

See comment

310 per 1000

129 per 1000(43 to 316)

Medium-risk population

310 per 1000

129 per 1000(43 to 316)

Episodes of superinfection or antimicrobial resistance

Study population

OR 0.29(0.09 to 0.92)

81 (1 study)

See comment

333 per 1000

126 per 1000(43 to 315)

Medium-risk population

333 per 1000

126 per 1000(43 to 315)

Duration of antibiotic therapy

See comment

See comment

Not estimable

81 (1 study)

See comment

Duration of ITU stay

See comment

See comment

Not estimable

81 (1 study)

See comment

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; ITU: intensive therapy unit; OR: odds ratio

GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Summary of findings 3. Discontinuation of antibiotics according to clinical guideline for hospital-acquired pneumonia in critically ill adults

Discontinuation of antibiotics according to clinical guideline for hospital-acquired pneumonia in critically ill adults

The mean duration of antibiotic therapy in the intervention groups was 2 lower(3.21 to 0.79 lower)

290 (1)

See comment

In-hospital mortality

Study population

OR 0.8(0.49 to 1.29)

290 (1)

See comment

371 per 1000

321 per 1000(224 to 432)

Medium-risk population

371 per 1000

321 per 1000(224 to 432)

Duration of ICU stay

The mean duration of ICU stay in the intervention groups was 0.2 lower(1.75 lower to 1.35 higher)

290 (1)

See comment

Duration of hospital stay

The mean duration of hospital stay in the intervention groups was 0.3 higher(3.63 lower to 4.23 higher)

290 (1)

See comment

Duration of mechanical ventilation

The mean duration of mechanical ventilation in the intervention groups was 0.3 lower(1.79 lower to 1.19 higher)

290 (1)

See comment

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; ICU: intensive care unit; OR: odds ratio

GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Summary of findings 4. Discontinuation of antibiotic therapy according to serum procalcitonin level for hospital-acquired pneumonia in critically ill adults

Discontinuation of antibiotic therapy according to serum procalcitonin level for hospital-acquired pneumonia in critically ill adults

Discontinuation of antibiotic therapy according to serum procalcitonin level

28-day mortality

Study population

OR 0.66(0.39 to 1.14)

308 (3 studies)

265 per 1000

192 per 1000(123 to 291)

Medium-risk population

258 per 1000

187 per 1000(119 to 284)

Recurrence of pneumonia

Study population

OR 2.06(0.74 to 5.7)

66 (1 study)

See comment

286 per 1000

452 per 1000(229 to 695)

Medium-risk population

286 per 1000

452 per 1000(229 to 695)

28-day antibiotic-free days

The mean 28-day antibiotic-free days in the intervention groups was 2.8 higher(1.39 to 4.21 higher)

167 (2 studies)

Duration of antibiotic therapydays

The mean duration of antibiotic therapy in the intervention groups was 3.2 lower(4.45 to 1.95 lower)

308 (3 studies)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; ICU: intensive care unit; OR: odds ratio

GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.